This invention relates to human pre-adipose cell lines capable to differentiate into adipose cells. In particular, the present invention pertains to pre-adipose cell lines derived from white adipose tissue and their use in developing drugs, food ingredients and supplements against obesity, diabetes and cardio-vascular diseases.
Obesity has been declared a public health hazard by the National Institutes of Health. Obesity may be defined as the presence of excess adipose tissue which affects about 30 to 50% of the North American population and a substantial percentage of the population worldwide. The effects of obesity, e.g. non-insulin dependent diabetes, coronary artery disease, and hypertension, are estimated to have resulted in $45.8 billion in direct costs and an additional $23 billion in indirect costs from, e.g., missed work.
It is held that excessive ingestion of fat and carbohydrate induces obesity and hyperlipidemia and even develops hypertension and arteriosclerosis ultimately. The desirability of repressing the absorption of fat and carbohydrate and diminishing the accumulation of fat has, therefore, been finding enthusiastic recognition. Infants, on exposure to excessive caloric intake, suffer increase of adipocytes and assume the state which may well be called potential obesity. By this reason, it has been reported that the repression of the increase of the number of adipocytes particularly in infants results directly in the prevention of the obesity and the cardiovascular diseases which may well be called complications of obesity in children and consequently in adults.
To combat this evident health problem, both prophylactic and therapeutic approaches are necessary. For prophylactic purposes, it would be useful to be able to predict and measure a person's propensity or susceptibility to obesity. For therapeutic purposes, a means for interfering with the development or differentiation of adipocytes (fat cells) would be of great benefit. None of these desired objectives has been achieved so far, which is mainly due to that little is known about the regulation and control of the development of adipose tissue, e.g. the proliferation and differentiation of adipocytes precursors.
The identification of means or substances, respectively, controlling such proliferation and differentiation is very important for understanding normal adipose tissue development and for designing approaches for controlling abnormal states of adipose tissue development such as obesity.
To determine whether a substance is involved in the physiological regulation of adipose tissue development, investigations may be carried out if adipocytes or precursors thereof are responsive to this factor and ultimately if this factor can efficiently and specifically modulate adipose tissue development in vivo. Appropriate studies could not be performed so far, which fact is mainly due to a lack of suitable tissue or cells derived from human adipose tissue exhibiting properties of normal adipocytes from living tissue and being capable to be cultured for a prolonged period in vitro so as to carry out the experiments.
Fat cells or adipocytes (adipose cells) the main cell population of fat tissue represent a principal storage depot for triglycerides, and are deemed to be endocrine cells. Adipose tissue provides an energy storage reserve for the body in the form of triglycerides and this tissue can release free fatty acids when caloric intake falls below metabolic needs. In response to increased dietary intake, the body will normally automatically increase energy expenditure through activity to maintain an energy balance. Energy can also be released as heat. There are common energy regulation pathways that balance dietary intake with metabolic activity largely mediated through the hypothalamus. It is now also apparent that the adipocytes play an active role in this process and likely produce molecules that serve to feed back and effect regulation of triglyceride metabolism. Furthermore, adipocytes are able to secrete hormones which modulate key functions in peripheric or central organs. The best example being the leptin secreted by adipocytes and regulating energy metabolism and satiety via receptors located in hypothalamus. It would therefore be of great interest to be capable to find and investigate such molecules.
There are essentially two types of adipose tissue, brown and white, which carry out quite different roles in the body. White adipose is designed to store excess caloric intake while brown adipose tissue uses a unique system to syphon off excess calories and use it to generate body heat. However, white adipocytes were shown to express uncoupling proteins involving the control of thermogenesis. Since only white adipose tissue subsists in adult humans, thermogenesis induced by white adipose may increase energy expenditure.